Stroke Secondary Prevention Flashcards
What is the strongest evidence for CEA (carotid endarterectomy) in the setting of stroke?
Best imaging modality for assessing carotid stenosis in setting of stroke?
CTA during acute stroke imaging work up - advantage over Doppler as shows good views of posterior circulation
Is there any evidence for asymptomatic CEA or indications outside of CVA?
No
Role of carotid stenting over CEA?
Some emerging data for potential equipoise between CEA and carotid stenting in < 70 year olds - see CREST trial and accompanying editorial Brott et al NEJM 2010; Davis and Donnan NEJM 2010
Where does the evidence for CEA in context of stroke come from?
3 large trials
- ECST
- NASCET
- VACSP
Benefit strongest in higher grade stenoses 70-99%
and the meta-analyses of these
See Cochrane Review 2011
Atrial fibrillation and anticoagulation - warfarin or DOAC (direct oral anticoagulant)?
DOACs have largely replaced warfarin for AC in setting of AF for stroke prevention
Exceptions to using warfarin for AC in setting of stroke prevention?
- mechanical heart valves
- ‘valvular’ AF
- significant renal impairment CrCl < 30 for Dabigatran and Rivaroxaban, and < 25 for Apixaban
Advantages of one DOAC over another for stroke prevention?
No head to head trials have been done so any advantages/comparisons are very indirect
No data at the moment to support any one over another
though there is the reversal considerations - e.g. now quite a lot of experience reversing Dabigatran with Idarucizumab (Praxbind) including in setting of acute stroke
Role of left atrial appendage closure?
Remains an option in patients with absolute contraindications to AC
How to give Idarucizumab to reverse Dabigatran
2x consecutive 2.5g pushes IV
Effect is almost immediate and sustained (12 hrs)
What about Andexanet alfa for reversal of Rivaroxaban?
Firstly, not available in Australia or NZ
Secondly, studies do not demonstrate a quick or sustained effect - so even if were available unlikely to be suitable for AC reversal pre- acute thrombolysis
Definition of valvular AF
AF with mechanical prosthetic heart valve or moderate to severe mitral stenosis
Is there any evidence for DOAC use in valvular AF?
Currently no
So far, Dabigatran shows inferior effectiveness and safety profile c.f. warfarin for mechanical heart valves
How long should we be monitoring people for to detect AF?
Current practice vs emerging evidence
Current practice is 24hr holter
- Crystal AF study 2014, however, showed that up to 30% of all patients with stroke eventually found to have AF if monitored for 3 years - likely that we need to monitor people for longer than is current practice but resource limitations - some hope on horizon with new devices e.g. ‘heart bug’, wearables
What is the current evidence for DAPT in the setting of minor stroke (low NIHSS) and high risk TIA (high ABCD2)?
Growing trend towards using DAPT in these cases - which is increasingly grounded on strong trial evidence that DAPT in these populations reduces recurrence CVA rates
- CHANCE (China 2013) - used Clopi LD 300mg, follow up 21 days, demonstrated reduced CVA recurrence rates in DAPT c.f. aspirin monotherapy. However Asian populations have known higher rates of intracranial atherosclerotic disease (ICA), so raised Qs whether this data is generalisable to Western popns. Sub-analysis of CHANCE trial also showed no difference in CVA recurrence in those without ICA
- POINT trial (NA, Europe Australia, NZ) used higher Clopi LD 600mg and followed up 90 days, however RE-DEMONSTRATED reduction in recurrent CVA rates. But most benefit is seen in first 30 days and beyond this not much change- and DAPT associated with a small but sig increased risk of major haemorrhage
So current guidelines recommend DAPT but for no longer than 1 month - after which patient should be continued on monotherapy
Evidence for the role of alternative antiplatelet agents in stroke and TIA?
Some evidence that Ticagrelor may be more effective at reducing recurrent stroke rates c.f. Clopidogrel
Like Clopidogrel, Ticagrelor inhibits the P2Y12 receptor on platelets but unlike Clopidogrel, Ticagrelor does not require hepatic activation - a process which is often deficient in some populations e.g. up to 60% Asian people are deficient in this process so are less responsive to Clopidogrel)
- CHANCE 2 trial (China 2021) comparing DAPT with Clopidogrel vs DAPT with Ticagrelor in patients with known CYP2C19 loss of function carriers - lower rate of CVA recurrence in Ticagrelor DAPT group (6) vs Clopi DAPT group (7.6) and no significant difference in rates of bleeding
- THALES trial evidence (2022) 11,000 patients - showed a small but statistically signficant reduction in CVA recurrence in those on dual Ticagrelor + Aspirin , cf. Aspirin monotherapy i.e. 5.1% in DAPT vs. 6.3% in mono (mainly driven by reduced ischaemic stroke)
Even within 30 days however, DAPT group had higher rate of bleeding
Evidence for lipid lowering therapy in stroke secondary prevention?
High dose statin is standard recommendation for patients post CVA or TIA - however beware tolerability issues
- SPARCL trial (2006) demonstrated strongest evidence for the above. Compared Atorvastatin 80mg with placebo group in patients with CVA or TIA (that were presumed from atherosclerotic cause) and raised LDL > 2.5 -> found that after 5 years of follow up risk of recurrent CVA was 11.2 vs 13.1% respectively (NNT 45)
Interestingly a post-hoc analysis of SPARCL trial also demonstrated small increase in haemorrhageic CVA in high dose statin group c.f. placebo -> hence why statins not recommended after ICH’s
- Growing evidence for PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors - a new class of drugs which lower LDL. E.g. Evolocumab, Alirocumab - currently in Australia approved for both familial and non-familial hypercholesterolaemia - WATCH THIS SPACE
- Treat Stroke To Target Trial (NEJM 2020) compared more aggressive LDL target < 1.8 with less aggressive target of 2.3-2.8 and found statistically signficant lower rate of major cardiovascular events in the aggressive target group (8.5%) c.f. with the less aggressive group (10.9%) - AND no differences in safety. Up to 9 yr follow up
(NB patients in this trial took a statin, ezetimibe or both)
Evidence for PFO (patent foramen ovale) closure?
- RESPECT trial (2013) - longest follow up to date
Measured ‘event-free’ probability in group treated with closure vs medical therapy - neutral in ITT but high drop out rate in medical therapy group (many people switched to closure) and per protocol analysis did find lower rates of recurrent CVA in patients with closure, and no diff in AF rates - GORE-REDUCE (2017) - reduction in stroke risk in closure group c.f. medical group; also showed a small increase in AF in closure group but this was mostly transient peri-procedural rather than prolonged AF
- CLOSE (2017) -reduced CVA risk in closure group Absolute Risk Reduction 4.5% in closure group (1 stroke avoided at 5 years for every 20 patients treated) slight increase in AF in closure group.
